chrX-13785650-C-A

Variant names:

• chrX-13785650-C-A
• rs144162602
• NM_001001995.3:c.340G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001995.3(GPM6B):​c.340G>T​(p.Ala114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPM6B NM_001001995.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14162615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3	c.340G>T	p.Ala114Ser	missense_variant	Exon 3 of 8	ENST00000316715.9	NP_001001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9	c.340G>T	p.Ala114Ser	missense_variant	Exon 3 of 8	2	NM_001001995.3	ENSP00000316861.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.5
DANN	Benign	0.89
DEOGEN2	Benign	0.30	.;.;.;.;T;T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.83	T;T;T;T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.8	.;.;.;.;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.040	N;N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.41	T;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T
Polyphen		0.0	.;B;B;B;B;.
Vest4		0.22
MutPred		0.52		.;.;Gain of relative solvent accessibility (P = 0.0166);.;.;.;
MVP		0.64
MPC		0.70
ClinPred		0.20	T
GERP RS		-2.0
Varity_R		0.065
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144162602; hg19: chrX-13803769;